dbSNP rs2989722: FCN1:c.271+115C>T (chr9-134914641-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002003.5(FCN1):c.271+115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 923,456 control chromosomes in the GnomAD database, including 162,056 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.52 ( 21997 hom., cov: 30)

Exomes 𝑓: 0.60 ( 140059 hom. )

Consequence

FCN1
NM_002003.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.00

Publications

2 publications found

Variant links:

Genes affected

FCN1 (HGNC:3623): (ficolin 1) The ficolin family of proteins are characterized by the presence of a leader peptide, a short N-terminal segment, followed by a collagen-like region, and a C-terminal fibrinogen-like domain. The collagen-like and the fibrinogen-like domains are also found separately in other proteins such as complement protein C1q, C-type lectins known as collectins, and tenascins. However, all these proteins recognize different targets, and are functionally distinct. Ficolin 1 encoded by FCN1 is predominantly expressed in the peripheral blood leukocytes, and has been postulated to function as a plasma protein with elastin-binding activity. [provided by RefSeq, Jul 2008]

FCN1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN1	NM_002003.5 link	c.271+115C>T		intron_variant	Intron 3 of 8	ENST00000371806.4	NP_001994.2	O00602

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN1	ENST00000371806.4 link	c.271+115C>T		intron_variant	Intron 3 of 8	1	NM_002003.5	ENSP00000360871.3		O00602

Frequencies

GnomAD3 genomes

AF:

0.523

AC:

79321

AN:

151704

Hom.:

22005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.788

Gnomad AMR

AF:

0.450

Gnomad ASJ

AF:

0.616

Gnomad EAS

AF:

0.429

Gnomad SAS

AF:

0.584

Gnomad FIN

AF:

0.657

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.624

Gnomad OTH

AF:

0.510

GnomAD4 exome

AF:

0.598

AC:

461595

AN:

771636

Hom.:

140059

AF XY:

0.601

AC XY:

238609

AN XY:

396742

show subpopulations

African (AFR)

AF:

0.339

AC:

6301

AN:

18614

American (AMR)

AF:

0.381

AC:

11482

AN:

30132

Ashkenazi Jewish (ASJ)

AF:

0.610

AC:

11435

AN:

18758

East Asian (EAS)

AF:

0.399

AC:

12975

AN:

32528

South Asian (SAS)

AF:

0.609

AC:

38115

AN:

62620

European-Finnish (FIN)

AF:

0.641

AC:

30226

AN:

47186

Middle Eastern (MID)

AF:

0.588

AC:

2115

AN:

3596

European-Non Finnish (NFE)

AF:

0.629

AC:

328056

AN:

521670

Other (OTH)

AF:

0.572

AC:

20890

AN:

36532

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

9927

19854

29782

39709

49636

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5996

11992

17988

23984

29980

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.523

AC:

79327

AN:

151820

Hom.:

21997

Cov.:

AF XY:

0.526

AC XY:

39039

AN XY:

74172

show subpopulations

African (AFR)

AF:

0.339

AC:

14052

AN:

41418

American (AMR)

AF:

0.450

AC:

6872

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.616

AC:

2135

AN:

3466

East Asian (EAS)

AF:

0.429

AC:

2190

AN:

5108

South Asian (SAS)

AF:

0.584

AC:

2804

AN:

4804

European-Finnish (FIN)

AF:

0.657

AC:

6927

AN:

10538

Middle Eastern (MID)

AF:

0.599

AC:

175

AN:

292

European-Non Finnish (NFE)

AF:

0.624

AC:

42388

AN:

67906

Other (OTH)

AF:

0.507

AC:

1067

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1801

3602

5403

7204

9005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

704

1408

2112

2816

3520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.443

Hom.:

1432

Bravo

AF:

0.494

Asia WGS

AF:

0.467

AC:

1625

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.62

(source)

DANN

Benign

0.34

PhyloP100

-2.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over